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Chapter 125 Molecular Basis of Platelet Function 1877

1. Tethering

Granule

Actin
cytoskeleton
Plasma
membrane

2. Docking
NSF
Rab GTPase
Mediators
PKC/Pleckstrin Granule
Ca 2

VAMP8
(vSNARE)
MUNC13–4
MUNC18b
STX11 (tSNAREs)
SNAP23

3. Fusion and Secretion MUNC13–4

MUNC18b

VAMP8
STX11

SNAP23

B Granule contents
Fig. 125.3, cont’d (B) MOLECULAR CONTROL OF GRANULE SECRETION. This is a schematic
diagram of steps in granule secretion. (1) Tethering: attachment of granules to the membrane cytoskeleton.
(2) Docking: the engagement of vSNAREs on the granule membrane and tSNAREs on the target membrane
to form a prefusion complex. In platelets, these docking proteins are VAMP8 on α granule and dense granule
membranes, STX11/SNAP-23 complex on the plasma membrane and accessory proteins Munc13-4 and
Munc18b/Munc18-2. (3) Fusion/secretion: involves the zippering of opposing SNAREs, applying force to
fuse the granule and plasma membranes, resulting in release of the granule contents. Additional mediators of
2+
this active process include Rab GTPases, PKC, pleckstrin, Ca , and NSF. β-TG, β-Thromboglobulin; CXCL,
CXC-chemokine ligand; EGF, epidermal growth factor; GP, glycoprotein; IgG, immunoglobulin G; NSF,
N-ethylmaleimide-sensitive factor; PAI-1, plasminogen activator inhibitor-1; PDGF, platelet-derived growth
factor; PF4, platelet factor 4; PKC, protein kinase C; RANTES, regulated upon activation, normal T-cell
expressed, and secreted; SNAP-23, synaptosomal-associated protein-23; SNARE, soluble N-ethylmaleimide–
sensitive factor attachment protein receptor; STX11, syntaxin 11; TGF-β, transforming growth factor-β;
tSNARE, target SNARE; VAMP8, vesicle-associated membrane protein 8; VEGF, vascular endothelial growth
factor; vSNARE, vesicle-associated SNARE; VWF, von Willebrand factor.